Sodium Benzoate, a Metabolite of Cinnamon and a Food Additive, Improves Cognitive Functions in Mice after Controlled Cortical Impact Injury

Int J Mol Sci. 2021 Dec 24;23(1):192. doi: 10.3390/ijms23010192.


Traumatic brain injury (TBI) is a major health concern, sometimes leading to long-term neurological disability, especially in children, young adults and war veterans. Although research investigators and clinicians have applied different treatment strategies or neurosurgical procedures to solve this health issue, we are still in need of an effective therapy to halt the pathogenesis of brain injury. Earlier, we reported that sodium benzoate (NaB), a metabolite of cinnamon and a Food and Drug Administration-approved drug against urea cycle disorders and glycine encephalopathy, protects neurons in animal models of Parkinson's disease and Alzheimer's disease. This study was undertaken to examine the therapeutic efficacy of NaB in a controlled cortical impact (CCI)-induced preclinical mouse model of TBI. Oral treatment with NaB, but not sodium formate (NaFO), was found to decrease the activation of microglia and astrocytes and to inhibit the expression of inducible nitric oxide synthase (iNOS) in the hippocampus and cortex of CCI-insulted mice. Further, administration of NaB also reduced the vascular damage and decreased the size of the lesion cavity in the brain of CCI-induced mice. Importantly, NaB-treated mice showed significant improvements in memory and locomotor functions as well as displaying a substantial reduction in depression-like behaviors. These results delineate a novel neuroprotective property of NaB, highlighting its possible therapeutic importance in TBI.

Keywords: TBI; glial activation; lesion cavity; memory and learning; sodium benzoate.

MeSH terms

  • Administration, Oral
  • Animals
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Astrocytes / pathology
  • Behavior, Animal / drug effects
  • Brain Injuries, Traumatic / physiopathology
  • Cerebral Cortex / injuries*
  • Cerebral Cortex / pathology
  • Cerebral Cortex / physiopathology*
  • Cinnamomum zeylanicum / chemistry*
  • Cognition / drug effects*
  • Disease Models, Animal
  • Food Additives / pharmacology*
  • Gait
  • Male
  • Memory / drug effects
  • Mice, Inbred C57BL
  • Motor Activity / drug effects
  • Neuroglia / drug effects
  • Neuroglia / metabolism
  • Rotarod Performance Test
  • Sodium Benzoate / administration & dosage
  • Sodium Benzoate / pharmacology*
  • Spatial Learning / drug effects


  • Food Additives
  • Sodium Benzoate